Prevalence of Alzheimer's Disease Pathology in the Community (HUNT4AD)

Prevalence of Alzheimer's Disease Pathology in a Large Norwegian Population-based Cohort and Predictive Power of Plasma p-tau217 and NfL.

The goal of this observational study is to (I) study the proportion of people with Alzheimer's disease pathology in a large Norwegian population-based cohort of people aged 70 years or older and to (II) study longitudinal changes of Alzheimer's disease pathology in the same population over a 14 year period.

The main aims are:

• What is the proportion of people with Alzheimer's disease pathology, defined by elevated plasma p-tau217, in a large Norwegian population-based cohort of people aged 70 years or older.
• What is the proportion of people with Alzheimer's disease pathology, defined by elevated plasma p-tau217, among those with normal cognition, mild cognitive impairment and dementia in a large Norwegian population-based cohort of people aged 70 years or older.
• What is the association between plasma p-tau217 concentration and mild cognitive impairment or dementia 4, 10 and 14 years later, respectively.
• What is the association between plasma NfL concentration and mild cognitive impairment or dementia 4, 10 and 14 years later, respectively.

Data is used from The Nord-Trøndelag Health Study (HUNT) wave 3 (2006-2008) and 4 (2017 - 2019, also including HUNT AiT 2021-2023).

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease; Mild Cognitive Impairment; Dementia of Alzheimer Type; Pathology; Biomarker in Early Diagnosis

• Study Type: Observational
• Enrollment (Actual): 9663

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The Nord-Trøndelag Health Study (HUNT) is carried out in the geographically defined area of Nord-Trøndelag i Norway and offers a good representation of the Norwegian population.

The HUNT study has invited the adult population in the area to participate in four waves: HUNT1 (1984 - 1986), HUNT2 (1995-1997), HUNT3 (2006 - 2008) and HUNT4 (2017 - 2019). HUNT4 70+ also included a follow-up, Ageing in Trøndelag (AiT) (2021 - 2023). Notably, the HUNT4 study recruited all people 70 + years of age from HUNT4 to participate in the study, HUNT4 70+.

Description

Inclusion Criteria:

• Living in the area of Nord-Trøndelag, where the HUNT study is carried out.
• Age 70 or older when participating in HUNT4
• Available blood sample from HUNT3, HUNT4 70+ or HUNT4 70+ AiT

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

The Trøndelag Health Study (The HUNT Study); (I) All participants from the HUNT4 70+ cohort (conducted 2017-2019, N=9,963) who have a blood sample (N=8,949). Participants underwent cognitive evaluation. (II) Selection of 3,948 participants from the HUNT3 cohort (conducted 2006-2008, n=8,548.). Selection criteria: Later participation in the HUNT4 70+ cohort or HUNT4 70+ AiT cohort and having an available blood sample in HUNT3. The 3,948 participants were further selected to include all those with a dementia diagnosis in HUNT4 70+ (N=approx. 1,100). Of the remaining HUNT3 participants included, 1/3 should have a diagnosis of normal cognition in HUNT4 70+, and 2/3 should have a diagnosis of mild cognitive impariment in HUNT4 70+. (III) All participants from the HUNT AiT cohort (Conducted 2021-2023, N=5,710) who have a blood sample. All HUNT4 70+ participants were invited to participate in HUNT4 AiT 4 years later. Participants underwent cognitive evaluation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma p-tau217 and NfL concentrations in the HUNT4 70+ cohort, HUNT4 AiT cohort and in selected participants from HUNT3	Concentration of plasma p-tau217 measured by Alzpath217 and plasma NfL measured by Neurology 4-plex E kit. For p-tau217, we will administer a cut-off previously derived from the Wisconsin Registry for Alzheimer's Prevention study to define particpants as amyloid positive, amyloid negative or in an intermediate range.	Biomarker concentration was measured in plasma samples from three time points: In the year 2006-2008, year 2017-2019 and year 2021-2023.
Association between concentrations of plasma p-tau217 and NfL with cognitive status	Association between concentrations of plasma p-tau217 and NfL with a clinical diagnosis of normal cognition, MCI and dementia in the HUNT4 70+ cohort and the HUNT4 AiT cohort	Cognitive examination and blood sampling was conducted at two time points: In the year 2017-2019 and year 2021-2023.
Predictive power of plasma p-tau217 and NfL	Reliability of plasma p-tau217 and NfL concentrations in HUNT3 and HUNT4 70+ for predicting cognitive impairment (I) measured by the MOCA in HUNT4 70+ and HUNT AiT, (II) defined by a clinical diagnosis of mild cognitive impairment or dementia in HUNT4 70+ and HUNT AiT.	14 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between kidney function and plasma p-tau217	What is the association between eGFR and plasma p-tau217 concentration in a large population-based cohort of older adults.	Cross-sectional measurements at three time points: In the year 2006-2008, year 2017-2019 and year 2021-2023. And longitudinal analysis (14 years, from 2006-2008 to 2021-2023))
Prevalence of amyloid pathology in different ApoE ε genotype groups	Proportion of study participants in HUNT4 70+ and HUNT4 AiT with amyloid pathology according to plasma p-tau217 in different ApoE ε genotype groups. Proportion of participants with amyloid pathology according to plasma p-tau217 among selected study participants in HUNT3 aged 60 to 69 years at study participation, differentiated by ApoE ε genotype groups. ApoE ε genotype status in participants has already been previously established.	Plasma p-tau217 was measured in plasma samples at three time points: In the year 2006-2008, year 2017-2019 and year 2021-2023.

Collaborators and Investigators

• Sponsor: Helse Stavanger HF
• Collaborators: Göteborg University; Norwegian University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2006
• Primary Completion (Actual): October 21, 2024
• Study Completion (Actual): October 21, 2024

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Estimated): December 5, 2024

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: cross-sectional; longitudinal; Population-based; NfL; Blood-based markers; p-tau217; Alzheimer's disease pathology
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease
• Other Study ID Numbers: 3870 (Other Identifier: Sisli Hamidiye Etfal Clinical Research Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: All researchers can apply for data at the HUNT research data senter.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No